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Fibrinolytic factors supports inflammation-induced colorectal carcinogenesis

Research Project

Project/Area Number 19K18104
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionJuntendo University

Principal Investigator

Munakata Shinya  順天堂大学, 医学部, 准教授 (50758761)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords潰瘍性大腸炎 / 大腸癌 / 繊維素溶解系 / プラスミン / 大腸がん / 線溶系 / 線維素溶解系
Outline of Research at the Start

本研究は近年増加傾向にある大腸癌に対し、高価な分子標的薬が市場に出回っている中で、線維素溶解系に着眼し、安価で安全な治療薬を提供する基礎研究である。これら線維素溶解系の代表であるプラスミンを含めたプロテアーゼ群の活性化が判明し、腫瘍抑制効果があることになれば、機序の解明されたがん予防薬ないし治療薬となりうる可能性がある。

Outline of Final Research Achievements

In a study using DSS / AOM, a mouse model of canceration of ulcerative colitis, a fibrinolytic inhibitor, plasmin inhibitor, led to suppression of canceration. This not only suppressed the activity of the MMP family through ectodomain shedding, but also suppressed the infiltration of tumor-associated macrophages by suppressing the degradation of the extracellular matrix. The EGF produced by this macrophage also suppressed the growth of the tumor by suppressing the ectodomain shedding, and suppressed the tumor growth ability in various aspects.

Academic Significance and Societal Importance of the Research Achievements

現在はマウスモデルでの制御であるが、今後、プラスミン阻害剤は安価な薬剤であるため、高騰する抗がん剤に加え、医療費抑制での貢献度も高い。全ては臨床試験の結果によるが、今後繊維素溶解系を用いた臨床試験での上乗せ効果を検証していきたい。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (8 results)

All 2021 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results)

  • [Journal Article] Angiopoietin-2 as a prognostic factor in patients with incurable stage IV colorectal cancer.2020

    • Author(s)
      Munakata S, Ueyama T, Ishihara H, Komiyama H, Tsukamoto R, Kawai M, Takahashi M, Kojima Y, Tomiki Y,
    • Journal Title

      J Gastrointest Cancer.

      Volume: 2020 Online ahead of print Issue: 1 Pages: 000-000

    • DOI

      10.1007/s12029-020-00392-1

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Creatine kinase elevation after robotic surgery for rectal cancer due to a prolonged lithotomy position2020

    • Author(s)
      Tsuchiya Yuki、Munakata Shinya、Tsukamoto Ryoichi、Okazawa Yu、Mizukoshi Kosuke、Sugimoto Kiichi、Takahashi Makoto、Tomiki Yutaka Kojima Yuichi、Sakamoto Kazuhiro
    • Journal Title

      BMC Surgery

      Volume: 20 Issue: 1

    • DOI

      10.1186/s12893-020-00771-2

    • Related Report
      2020 Research-status Report
  • [Presentation] 新規開閉型人工肛門装具の開発2021

    • Author(s)
      宗像慎也
    • Organizer
      日本外科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Impact of left colonic artery preservation on anastomotic leakage in laparoscopic sigmoid resection for sigmoid colon cancer2020

    • Author(s)
      宗像慎也
    • Organizer
      日本内視鏡外科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 線維素溶解系からみたColitic cancer増殖機構の解明2020

    • Author(s)
      宗像慎也
    • Organizer
      日本消化器病学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Proteolytic niche2020

    • Author(s)
      宗像慎也
    • Organizer
      日本外科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 回腸ろう造設におけるHigh outputの腸内細菌そうの解析2020

    • Author(s)
      宗像慎也
    • Organizer
      日本消化器外科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 線維素溶解系からみたColitic cancer増殖機構の解明2019

    • Author(s)
      宗像慎也
    • Organizer
      日本大腸肛門病学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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